Pharmaceutical Granules

• Granules are solid oral dosage forms that can be taken directly or used as intermediates for other pharmaceutical products like hard gelatin capsules and tablets.
• Granules meant for direct oral consumption consist of small, solid, dry, fragile, porous particles with no regular geometric shape
• The particles are close to spherical, rod-shaped, or cylindrical and range in diameter from 0.5-2 mm
• Granules contain one or more active ingredients and auxiliary substances like diluents, binders, disintegrants, flavorings, and colorants.
• The auxiliary substances used are added depending on the need

Purpose of Granulation

• Prevents the components from separating because of differences in size and density

• Improves the flow of powders for consistent filling

• Enhances compressibility of powders

• Minimizes dust and worker contamination

• Granules are denser and take up less space than powders

• Granules are packaged as single doses in sachets or paper packets, or in multidose containers with a measuring tool to dispense the prescribed amount

• Types are uncoated, effervescent, soluble for liquid preparation, and film-coated

Effervescent Granules

• Uncoated granules containing an effervescent couple, made up of an organic acid, such as citric or tartaric acid, and a salt of carbonic acid with a strong base, such as carbonate or bicarbonate

• The effervescent couple reacts quickly when water is present.

• Carbonic acid that decomposes into water and releases carbon dioxide gas (CO2), resulting in the active ingredient dispersing or dissolving in the fluid, used by mixing the granules in a glass of water and consuming only after the release of carbon dioxide gas.

Coated Granules

• Granules covered with a thin, continuous layer of a film-forming polymer
• The film coating dissolves in the stomach and releases the coated substance
• Coating protects the active ingredients from external factors like humidity and oxygen

Gastro-Resistant Granules

• Prepared by coating granules with a thin layer of a film-forming polymer that resists gastric fluid, dissolves in intestinal fluid, and releases the active ingredient in the intestines

Modified-Release Granules

• Made by coating granules, or consist of an active ingredient and a sustained-release excipient (film former or fatty substance)

• These granules are designed to control the rate or location at which their active components are released.

• Uncoated granules and granules coated with modified-release layers can be ingested as is, placed in hard gelatin capsules, or made into tablets

• This is done to change how quickly the active ingredient is released to regulate where the active ingredients are released

Preparing Granules

• The formula's ingredients are first mixed until they are homogenous, then the powder mixture is formed into a cohesive mass that is then broken up into smaller, fragmented pieces known as granules
• This is achieved through dry or wet granulation

Dry Mixing Powders

• Mixing powders is a common initial step in making solid pharmaceutical forms, like powders, granules, capsules etc
• Mixing is essential because it ensures the drug is evenly distributed throughout the final product
• Drying ingredients with high moisture content before weighing to achieve the desired moisture level when using direct compression for effervescent tablets
• This prevents the degradation of moisture-sensitive materials and prevents the effervescent couple from reacting prematurely
• Grinding some of the mixture's ingredients might be needed to to get a fine powder with consistent particle sizes in line with the dimensions of the other ingredients
• Sieving the mixture components using a suitable sieve is done to eliminate lumps, standardize particle sizes, improve mixing, and make sure all of the components is weighed accurately
• Obtaining a homogenous mixture is vital in mixing because it guarantees that each part has all the ingredients in the same ratios as in the mix, this affects how well the dosage performs, and several factors determine how well the mixing occurs.

Factors affecting Powder Homogeneity

• Electrostatic charges that build up on the powder's surface because of the particles rubbing against one another and which causes the tiny bits to clump together, lowers how well they flow, and produces a mix that isn't consistent
• The shape of the components has a big impact and spherical or multi-sided powder mixes more quickly than needle-shaped or plate-like powders with less movement in the mixer
• The mixing is quicker when the powder particles have comparable sizes and densities, however, if the density or size varies significantly, the mixture has trouble becoming consistent
• The texture of the surfaces of the blended components greatly influences how well the completed combination mixes so smooth textures improves the mixing's effectiveness but rough textures affect the product negatively
• For mixing a tiny quantity of one substance with other substances, adding the lesser amount to the remaining combination is preferable to putting static-electricity-caused clumps of the substance into a moving mixture while sieving very finely

Mixers

• The type of mixer used, how full the mixer is with powders, how fast the mixer runs, and how long it mixes affect the powder
• Common mixers include rotating cube mixers, septal mixers, conical mixers, and planetary mixers.

Rotating cube mixer

• The equipment has rectangular cube made of stainless steel with a rotating axis between two opposing heads
• This axis has arms that help improve how well mixing happens and the complete device is powered by a varied-speed motor and differ to how the inner axis holding the arms rotate

Septal Mixer

• It is made up of two cylinders that are linked at one end to create a V or Y shape with a 90-degree angle
• This device is secured to a rotating axis in addition to having arms to improve the mixer's efficiency.
• The mixer's movement ensures that the mixture either separates or combines into one

Conical Mixer

• The machine has two cones joined at their bases
• It has metal pieces inside to mix the powder while turning, with a rotating container to swirl the mix at regulated speeds around in circles within a cylindrical receptacle

Orbital Mixers with agitators

• The stirrers rotate at variable rates inside a stainless-steel bowl, and each stirrer can be changed based on the material's viscosity and combining requirements, liquid, solid mixing, and/or doughy substance
• In this device, the impeller moves while the basin remains in place, which is distinct from the other three already mentioned units is used

Methods of Granulation

Dry Granulating

• This method is used when the granule, tablet, or capsule ingredients are sensitive to moisture and heat, have adhesive qualities that make granulation easier, and include the following techniques.

Double Compression method

• Powders are subjected to high pressure after being combined with functional excipients using an appropriate tablet press designed with large in diameter pistons

• The press is has poor movement properties, a rotating press that produces hefty impact pressure is favored instead

• Break the large tablet slugs, into particles using a suitable mill or oscillating granulator and sieve the resulting granules to ensure consistent particle sizes

• The initial compression causes a problem with entrapped air, which is a core issue that is encountered

• Greater space between the upper and lower pistons in the cylinders makes it easier for air to become caught in between, pressure is dropped, speed is reduced, and chamber fill is reduced when the pistons are spaced wider apart

• Adding dry binding excipient could enhance method since delicate granules that aren't very resistant are made

Compacting Method

• Using this technique, the materials are compacted by laminating by pushing them between two counter-rotating cylinders and then crushing sheets and homogenizing the materials

• Compactor Mill, uses a screw placed in a feeding funnel inside the machine's housing and then breaks and standardizes using the same dimensions as before while compressing

• Available is a full machine that can apply the powder to its surface, crush the powder using the mounting studs in machine under the openings

• Granulation through a single appliance is made possible by running powder through this machine

• Though this technique provides good results, it also has several significant drawbacks.

• The equipment that is used is quite expensive, the ability to adjust or control is complex, we obtain a high percentage of fine powders after grinding, the formed sheets, the disintegration period, and compressability

Le fritage/Fusion

• Putting all the different parts of the tablets or materials called blend them together and expose them to heat

• This process causes the water of crystallization (e.g., citric acid) to come out, which in turn dissolves the water-soluble binding agent

• The mixture that is formed by compacting powders then passes through a sieve and is dried in a suitable oven

• The mixer and sieving gear should continue as during the moist granule process, but the heat applied by heat equipment maintains

• The technique can be continued in a standard oven or using specific mixers like ones that are made larger-than-usual Lodige models because the contact produced heats the device

Wet Granulation Method

• A liquid is mixed with the powders, this liquid it can dissolve that helps binding a mass that is made, the mass is dried

• Sometimes, it doesn't come together so an extra binding is needed in the ingredient

• The binders used in a mixing machine are materials with solubility in the water when the medicine is not, use alcohol

• The technique makes the components of blending in an easier way which the attributes whether dusty is used

Ameliorations include:

• Less steps
• Spillage decreases

Granules are solid oral dosage forms used directly or as intermediates for products like capsules and tablets. They consist of small, dry particles without a regular shape, containing active ingredients and auxiliary substances. Granulation prevents component separation, improves flow and compressibility, minimizes dust, and saves space compared to powders.